Diagnosis Of Chronic Granulomatous Disease Research Articles

Diagnosis of Chronic Granulomatous Disease: Strengths and Challenges in the Genomic Era.

Chronic granulomatous disease (CGD) is a group of rare primary inborn errors of immunity characterised by a defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective and inflammatory complications. Despite recent advances in our understanding of the genetic and molecular pathophysiology of X-linked and autosomal recessive CGD, and growth in the availability of functional and genetic testing, there remain significant barriers to early and accurate diagnosis. In the current review, we provide an up-to-date summary of CGD pathophysiology, underpinning current methods of diagnostic testing for CGD and closely related disorders. We present an overview of the benefits of early diagnosis and when to suspect and test for CGD. We discuss current and historical methods for functional testing of NADPH oxidase activity, as well as assays for measuring protein expression of NADPH oxidase subunits. Lastly, we focus on genetic and genomic methods employed to diagnose CGD, including gene-targeted panels, comprehensive genomic testing and ancillary methods. Throughout, we highlight general limitations of testing, and caveats specific to interpretation of results in the context of CGD and related disorders, and provide an outlook for newborn screening and the future.

A CASE OF ACUTE CORONARY SYNDROME UNDER IMMUNSUPRESSION WHO IS THE CRIMINAL NEUTROPHILS OR T CELLS?

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by recurrent, life-threatening bacterial and fungal infections of the skin, airways, lymph nodes, liver, brain, and bones. These infections most commonly occur in organs in contact with the outside world (lungs, gastrointestinal tract, and skin), as well as in lymph nodes that drain these structures. While involvement can be seen in many organs, there is no known cardiovascular involvement. Our case is an ACS case that has a different place in the literature because acute coronary syndrome (ACS) was seen in a 20-year-old male patient with a diagnosis of chronic granulomatous disease.

Carrier State of Chronic Granulomatous Disease Presented at Middle Age: A Case Report

Introduction: Chronic granulomatous disease (CGD) is the most common inherited defect of phagocytes. Although most female carriers of X-linked CGD have been considered to be unaffected, they may have similar problems to those of CGD patients. This study suggests that the CGD carrier state might be more complex than it was previously appreciated. Case Presentation: A sixty-year-old woman visited our hospital in June 2021 due to pneumonia and pleural effusion. Chest computed tomography scan revealed left lower lobe pneumonia and mediastinal lymphadenopathies. In July 2021, her symptoms (high-grade fever, chills, and hemoptysis) were initially attributed to a hydatid cyst. Therefore, she underwent a lobectomy, resulting in purulent drainage on the excision site on the skin, refractory to local and systemic treatments. The refractory and recurrent nature of the lesions led to the immunological evaluation, which was completely normal with a 100% nitroblue tetrazolium (NBT) and a dihydrorhodamine (DHR) of 278 (normal > 100). Further DHR123 flow cytometry investigations with multiple stimulants revealed a carrier state of CGD, which was relevant to her history of chronic complications. Conclusions: Adult patients with unusual manifestations suggestive of neutrophil function defects in adulthood should be evaluated for the CGD carrier state. In these cases, NBT alone may miss the diagnosis of CGD. In such cases, DHR testing with multiple stimulants may establish a robust diagnosis.

Infections due to Salmonella sp. in children with chronic granulomatous disease: Our experience from North India

Infections with non-typhoidal Salmonella sp. have been documented in children with chronic granulomatous disease (CGD), but the prevalence of salmonella infection in children with CGD in underdeveloped countries is unknown. We assessed the clinical profiles of CGD patients diagnosed at our tertiary care centre in north India and had Salmonella sp.infections. We found three patients with Salmonella sp. bloodstream infections (2-proven, 1-probable) among the 99 CGD patients. After receiving cotrimoxazole prophylaxis following a CGD diagnosis, we noted that none of our patients experienced non-typhoidal salmonella infection. One patient experienced severe typhoidal bacteremia despite receipt of cotrimoxazole prophylaxis. This patient required numerous hospital admissions and prolonged intravenous antibiotic regimen. We suggest that vaccination with killed typhoidal vaccines should be regularly given to children with CGD in order to avoid typhoidal bacteremia, in addition to cotrimoxazole prophylaxis and a focus on good hand and food hygiene.

Chronic Granulomatous Disease: a Cohort of 173 Patients—10-Years Single Center Experience from Egypt

PurposeChronic granulomatous disease (CGD) is an inherited primary immunodeficiency disorder of phagocytes, characterized by recurrent fungal and bacterial infections. Our aim is to describe the different clinical presentations, non-infectious auto-inflammatory features, types and sites of infections, and to estimate the mortality among our large cohort.MethodsThis is a retrospective study conducted at the Pediatric Department of Cairo University Children’s Hospital in Egypt, including cases with a confirmed CGD diagnosis.ResultsOne hundred seventy-three confirmed CGD patients were included. AR-CGD was diagnosed in 132 patients (76.3%) including 83 patients (48%) with p47phox defect, 44 patients (25.4%) with p22phox defect, and 5 patients (2.9%) with p67phox defect. XL-CGD was diagnosed in 25 patients (14.4%). The most common recorded clinical manifestations were deep-seated abscesses and pneumonia. Gram-negative bacteria and Aspergillus were the most frequently isolated species. Regarding the outcome, 36 patients (20.8%) were lost from follow-up. Among patients with known outcome, 94/137 patients (68.6%) are living, while 43/137 patients (31.4%) died.ConclusionAR-CGD is predominant in Egypt; CGD must always be ruled out in any patient presenting with typical or atypical mycobacterial or BCG-disease.

#2950 IGA NEPHROPATHY: PUTTING THE A IN THE UNACQUAINTED

Abstract Background and Aims IgA nephropathy (IgAN) is a common glomerulonephritis. Rarely it can be associated with other diseases and screening for these associations can be missed. We present 2 cases diagnosed as IgAN which were associated with rare underlying conditions. The first (patient X) is a 51-year-old female, who presented with new onset haematoproteinuria on a background of inflammatory arthritis, interstitial lung disease (ILD) and a recurrent maculopapular rash. The second case (patient Y) is a 34-year-old male, who presented with unexplained rapidly progressive chronic kidney disease and proteinuria. He had a background of hidradenitis suppurativa, acne rosacea, Crohn's disease and recurrent infections. Method X's immunology was negative aside from a weakly positive ANA and p-ANCA but negative ELISA. Her myositis panel was positive for PM/ScL antibody. Imaging showed multifocal ground glass opacification, consistent with ILD. Her renal function was normal, but renal histology demonstrated IgAN, without evidence of vasculitis. With these findings in mind, a diagnosis of anti-synthetase syndrome (AS) with IgAN was proposed. Y, conversely, had abnormal renal function, with significant proteinuria. Immunology screen was unremarkable other than a raised serum IgA, weakly positive MPO and equivocal PR3. Renal biopsy showed IgAN with severe interstitial fibrosis and tubular atrophy, and over 50% sclerosed glomeruli. Y later developed haemolytic anaemia; his neutrophil oxidase activity was absent, raising the possible diagnosis of chronic granulomatous disease (CGD). This was subsequently confirmed with genetic testing demonstrating an autosomal recessive gene for CGD. Results Both X's proteinuria and symptomatic burden significantly improved with methotrexate. Y was commenced on antibiotics and antifungals in light of the heightened risk of infection which CGD carries. He is now on maintenance haemodialysis. The only curative treatment for CGD is allogenic hematopoietic stem cell transplantation from a matched donor, for which he is being considered. Conclusion AS is a poorly defined, rare syndrome characterised clinically by ILD, arthritis and myositis. It is immunologically characterised by autoantibodies against aminoacyl tRNA synthetases; whilst X did not test positive, this does not preclude AS, as autoantibody titres fluctuate depending on disease activity [1]. Renal involvement in AS is extremely rare, or so the data would suggest. Couvrat-Desvergnes et al. examined 14 biopsies of patients with inflammatory myopathies plus renal involvement. Only 3 had AS; of these, 2 had IgAN. Other cases of IgA are described only in case reports. In all cases, immunosuppressive treatments were effective in achieving remission. Some cases describe other renal implications in AS, namely TMA and amyloidosis (Table 1). CGD is a rare primary immunodeficiency caused by genetic defects in the NADPH oxidase complex, which is critical in the destruction of phagocytes. Consequently, patients have recurrent infections and abnormal inflammatory responses result in granuloma formation. The incidence of renal disease in CGD has been suggested by some papers as being as low as 2.7% [2]. From review of the other cases of CGD with associated IgAN, it seems the patient we present is the oldest (Table 2). Interestingly, only 1 other case reports glomerulonephritis as the presenting complaint for CGD [3]. These cases highlight that, while IgAN is a disease in its own right, its diagnosis may shine light on other associated pathologies. It is crucial for nephrologists to be aware of rare associations as often it has impact on further management.

CRISPR-gene-engineered CYBB knock-out PLB-985 cells, a useful model to study functional impact of X-linked chronic granulomatous disease mutations: application to the G412E X91+-CGD mutation.

Chronic granulomatous disease (CGD) is a rare primary immune disorder caused by mutations in one of the five subunits of the NADPH oxidase complex expressed in phagocytes. Two-thirds of CGD cases are caused by mutations in CYBB that encodes NOX2 or gp91phox. Some rare X91+-CGD point mutations lead to a loss of function but with a normal expression of the mutated NOX2 protein. It is therefore necessary to ensure that this mutation is indeed responsible for the loss of activity in order to make a safe diagnosis for genetic counselling. We previously used the X-CGD PLB-985 cell model of M.C. Dinauer obtained by homologous recombination in the original PLB-985 human myeloid cell line, in order to study the functional impact of such mutations. Although the PLB-985 cell line was originally described by K.A. Tucker et al. in1987 as a distinct cell line isolated from a patient with acute nonlymphocytic leukemia, it is actually identified as a subclone of the HL-60 cells. In order to use a cellular model that meets the quality standard for the functional study of X91+-CGD mutations in CGD diagnosis, we developed our own model using the CRISPR-Cas9 technology in a certified PLB-985 cell line from DSMZ-German Collection of Microorganisms and Cell Cultures. Thanks to this new X-CGD model, we demonstrated that the G412E mutation in NOX2 found in a X91+-CGD patient prohibits access of the electron donor NADPH to its binding site explaining the absence of superoxide production in his neutrophils.

P147 Fungal osteomyelitis in patients with chronic granulomatous disease: a case series from a tertiary care medical centre.

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM ObjectivesTo present details of a case series of fungal osteomyelitis initially misdiagnosed as disseminated tuberculosis, in pediatric patients with chronic granulomatous disease.MethodInformed consent was obtained from the parents of three children (known cases of chronic granulomatous disease) with clinical features suggestive of chronic osteomyelitis. Clinical history was collected by interview and chart review. Samples were sent to the mycology laboratory for direct microscopy and fungal culture. Following a diagnosis of fungal osteomyelitis, antifungal therapy was administered and patients were monitored till discharge.ResultsFirst case:The first patient presented with fever, cough and progressive painful swelling over the left lower chest, and a past history of recurrent pneumonia and cervical lymphadenopathy, which were previously empirically treated with anti-tubercular therapy (ATT) and broad-spectrum antibiotics. Imaging revealed a soft tissue abscess with underlying rib osteomyelitis and pulmonary consolidation. Pus samples showed hyaline septate hyphae in direct microscopy and growth of Aspergillus nidulans in culture. The patient was successfully treated with intravenous voriconazole, which was switched to oral formulation on discharge.Second case:The second patient presented with fever and post-auricular swelling with multiple discharging sinuses, and a past history of fever and hilar lymphadenopathy, which were previously empirically treated with ATT and broad-spectrum antibiotics. Imaging revealed osteomyelitis involving mandible, temporal bone and skull base, with underlying sigmoid sinus thrombosis. Pus and tissue samples showed hyaline septate hyphae in direct microscopy and growth of Aspergillus fumigatus in culture. The patient was successfully treated with a combination of intravenous voriconazole and liposomal amphotericin B, and discharged on oral posaconazole.Third case:The third patient presented with progressive painful swelling over the right upper chest, and a past history of pneumonia, hemoptysis, and mediastinal lymphadenopathy, which were previously empirically treated with ATT and broad-spectrum antibiotics. During a previous hospitalization, imaging showed features suggestive of fungal pneumonia; BAL showed hyaline septate hyphae in direct microscopy and growth of Aspergillus fumigatus and Aspergillus flavus in culture, providing a diagnosis of fungal pneumonia which was treated with voriconazole and liposomal amphotericin B. During the present admission, imaging of the chest lesion revealed pus collection with underlying rib osteomyelitis, communicating with a cavity in the middle lobe of the right lung. FNAC from the lesion showed hyaline septate hyphae in direct microscopy but no growth in culture (probably due to previous antifungal therapy). The patient was successfully treated with a combination of intravenous voriconazole and liposomal amphotericin B, and discharged on oral posaconazole.ConclusionsFungal pneumonia and fungal osteomyelitis are often misdiagnosed as tuberculosis or bacterial infections, leading to unnecessary and ineffective ATT or broad-spectrum antibiotics. A high index of suspicion for fungal osteomyelitis is required in pediatric patients with a history of recurrent/chronic soft tissue infections, preceded by febrile episodes and/or pneumonia, especially if a diagnosis of chronic granulomatous disease (CGD) has already been established; if not, this characteristic clinical picture should in fact warrant evaluation for CGD.

Liver abscesses in the Western pediatric population.

Liver abscesses are rare in the Western pediatric population and data on predisposing factors and etiology are scarce. We aimed to describe predisposing factors, microbiological characteristics, and treatment. Retrospective analysis of children admitted to two tertiary care hospitals in Belgium from 1 January 1996 to 31 December 2019. We analyzed clinical features, predisposing factors, imaging characteristics, microbiological data, treatment, and outcome in children with a liver abscess and compared these data with the literature. We collected 24 cases with a male to female ratio of 1.4 and a median age of 3.2 years at time of diagnosis. Survival was 95.8%. Invasive culture specimens were obtained in 83.3% and showed growth of bacteria in 55%. Parenteral antibiotics were administered before invasive culture sampling in 80%. Liver abscesses were cryptogenic in four (16.7%) patients. Hepatobiliary disease was the most prevalent predisposing factor (n = 6; 25%), followed by recent antineoplastic therapy for malignancies (n = 5; 20.8%), intra-abdominal surgical pathology (n = 4; 16.7%) and umbilical venous catheters (n = 2; 8.3%). In two patients there was a parasitic origin (n = 2; 8.3%) and in one it was caused by Bartonellosis. There was no diagnosis of chronic granulomatous disease (CGD) in our cohort. Pediatric liver abscesses have a favorable outcome in the developed world. Whenever feasible, invasive abscess culture specimens should be obtained. In patients presenting with a cryptogenic liver abscess or atypical disease course, immunological workup should be ensured.

Protein kinase C Delta Deficiency should be in the differential diagnosis of Chronic Granulomatous Disease

Deficiency of any of the five NADPH oxidase complex components (CYBB, CYBA, NCF1, NCF2 and NCF4) causes chronic granulomatous disease (CGD), a genetic immunodeficiency characterized by severe neutrophil dysfunction and increased susceptibility to infections. The essential role of protein kinase C Delta (PRKCD) for oxidative burst in neutrophils was recently demonstrated. Here we present a child who presented with symptoms and infections considered diagnostic of CGD, and found to have PRCKCD deficiency.

Difficulties in diagnosis of chronic granulomatous disease in a 10-year-old child

Objective: to familiarize doctors with one of the rare variants of primary immunodeficiency – chronic granulomatous disease. The authors present a case of late diagnosis of chronic granulomatous disease in a 10-year-old child. The doctors missed the development of complications after BCG vaccination in the form of axillary lymphadenitis on the left (BCGitis), which led to the development of disseminated BCG infection, regarded as an infectious tuberculous process. The onset of chronic granulomatous disease occurred at the age of 10 months (paraproctitis complicated by an anal fistula). The assumption of the presence of immunodeficiency arose in connection with the recurrent course of pneumonia at the age of 4-5 years, but was regarded as a manifestation of a tuberculous infectious process. At the age of 8, during the protracted course of nonspecific polysegmental pneumonia, primary immunodeficiency without specific clinical form was diagnosed on the basis of the results of a comprehensive immunological examination. At the age of 10, chronic granulomatous disease was verified using a study of spontaneous and stimulated chemiluminescence of neutrophils and the results of a genetic study.

Chronic Granulomatous Disease With Inflammatory Bowel Disease: Clinical Presentation, Treatment, and Outcomes From the USIDNET Registry

Chronic granulomatous disease (CGD) is an inborn error of immunity caused by defects in the phagocytic nicotinamide adenine dinucleotide phosphate oxidase complex, leading to increased susceptibility to infection and inflammatory autoimmune diseases. Up to 50% of patients have gastrointestinal (GI) involvement and meet diagnostic criteria for inflammatory bowel disease (CGD-IBD). We analyzed patients with CGD from the US Immunodeficiency Network (USIDNET) registry to determine whether IBD changes the presentation, treatment, and outcomes of patients with CGD. A retrospective evaluation of CGD cases from the USIDNET registry was completed. CGD-IBD was defined as the presence of any major physician-reported inflammatory, noninfectious GI disease manifestation. Demographic information, conditions, infections, antimicrobial therapies, immunomodulator use, and hematopoietic stem cell transplantation data were analyzed. Of 194 patients with a diagnosis of CGD, 96 met criteria for IBD and 98 were categorized in the non-IBD group. Patients with CGD-IBD had an increased rate of infection compared with the non-IBD group (0.66 vs 0.36 infections/patient/year). Enteric organism infections were more common in patients with IBD. Immunomodulators were used at a significantly higher percentage in patients with IBD compared with patients without IBD (80% vs 56%, P < .001). Of the entire CGD cohort, 17 patients died (8.8%), with no significant difference between patients with IBD and patients without IBD (P= 1.00). Infectious events, enteric organism infections, and use of immunomodulatory drugs were higher in patients with IBD than patients without IBD; however, mortality was not increased. Patients with CGD and concurrent IBD are at increased risk for disease complications, supporting the importance of early recognition, diagnosis, and treatment.

A fludarabine and melphalan reduced-intensity conditioning regimen for HSCT in fifteen chronic granulomatous disease patients and a literature review.

Chronic granulomatous disease (CGD) is a life-threatening immunodeficiency condition. To date, hematopoietic stem cell transplantation (HSCT) is the only curative modality. We prospectively studied the outcomes of fifteen CGD patients undergoing HSCT with fludarabine and melphalan plus anti-thymocyte globulin (ATG). Most of the donors were fully matched siblings (n = 12). Cyclosporine A and methylprednisolone were used for graft-versus-host disease (GVHD) prophylaxis. CGD diagnosis had been suspected upon clinical symptoms and was confirmed in all patients by an abnormal neutrophil functional assay. The three-year overall survival (OS) and event-free survival (EFS) rates were 73.3% and 46.7%, respectively. With the median follow-up time of 33.12months, the mean OS and EFS were 42.6 and 26.8months; respectively. Eleven patients (73.33%) achieved full donor chimerism. Two stable mixed chimerisms with no sign of the underlying disease (13.33%) and two secondary graft failure (13.33%) occurred as well. The cumulative incidence of transplant-related mortality was 23.1% and it was two times more in adults compared with children. Three years GVHD-FS (free survival) was 57.8% in all patients and it was 70% and 42.9% in children and adults, respectively. Our results indicate that fludarabine, melphalan, and ATG have relatively favorable outcomes in CGD patients. Also, we suggest that HSCT should be performed as soon as a suitably matched donor is found.

Persistent Pneumonia in an Infant

An eight month old boy presented with a subacute febrile illness and radiological evidence of multifocal cavitatory consolidations in the lungs. He continued to worsen despite multiple oral and intravenous antibiotics. Preterminally, he developed respiratory distress, hepatosplenomegaly, bicytopenia, and hepatic dysfunction. Investigation for cause of persistent pneumonia resulted in a diagnosis of chronic granulomatous disease on the basis of Dihydrorhodamine assay and genetic analysis. Postmortem blood culture grew Burkholderia cenocepacia. Autopsy revealed necrotizing granulomatous inflammation with massive necrosis and abscesses in bilateral lungs. No organism could be identified by traditional stains on autopsy. Conventional PCR targeting 16S ribosomal DNA yielded Nocardia pseudobrasiliensis. In conclusion, an unusual course of pneumonia warrants invasive investigations for isolation of underlying organism, which not only provides guidance to choice of antimicrobials but also provides clue to an underlying disease.

Utility of Immunohistochemistry and Immunofluorescence in Determining the Pathogenic Variants of Chronic Granulomatous Disease.

Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder of phagocytes due to defects in any of the five subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. An initial diagnosis of CGD is made by flow cytometry-based dihydrorhodamine assay or nitro blue tetrazolium test, which is further confirmed by molecular assays. Expression of five subunits of NADPH oxidase components by either flow cytometric or western blot analysis provides clues toward the potential gene targets which are subsequently confirmed by various genetic assays. Immunohistochemistry (IHC) and immunofluorescence (IF) have never been earlier used to determine the expression of different subunits of NADPH oxidase system. We evaluated the utility of IHC and IF in determining the underlying pathogenic variants of CGD. Twelve genetically confirmed cases of CGD, comprising of biopsy specimens (n = 6), tissue blocks from autopsy cases (n = 3), and cellblocks of cell pellet prepared from peripheral blood (n = 4) were included. IHC for p67phox and p47phox subunits and IF for cytochrome b558 were performed. All 4 cases with pathogenic variation of NCF2 gene showed loss of expression for p67phox subunit. Two cases with pathogenic variation of NCF1 gene showed loss of expression for p47phox subunit. Five cases, except a single case with CYBB gene pathogenic variation, showed loss of expression for cytochrome b558 on IF. Thus, loss of expression consistently matched with the underlying genetic defects assessed by sequencing. Our results confirm our hypothesis that IHC and IF are two rapid, economical, pathologist-friendly techniques providing pertinent information regarding the underlying pathogenic variants and such immuno-analysis can be easily performed on the tissue.

Clinical features and early diagnostic clues of chronic granulomatous disease

Objective: To explore the early clinical clues for diagnosis of chronic granulomatous disease (CGD). Methods: One hundred and thirty-nine children with CGD seen in Beijing Children's Hospital from January 2007 to October 2020 were included in this study. The clinical features including age of onset, first presentations, reason for being hospitalized, etiology, imaging features, clues for early diagnosis of all patients were evaluated retrospectively. According to the time of diagnosis, the patients were divided into two groups, cases diagnosed before 2015 and after 2015 and 2015. The time of diagnosis, the length of stay and the hospital charges were compared between the two groups. T test and χ2 test were used for statistical analyses. Results: One hundred and nineteen of the cases were males and 20 were females. The age of onset was 4 months (8 d to 14 years), and 103 cases (74.1%) had onset before 1 year of age. The age at diagnosis was 1.8 years (21 d to 14.7 years), and the time of diagnosis delay was 1 year (7 d to 13.7 years). One hundred and thirty-five cases (97.1%) had pulmonary infection as the main reason for hospitalization, of whom 76 cases (56.3%) had positive pulmonary etiology. One hundred and thirty-six patients (97.8%) were referred cases, of whom 5 were suspected of CGD before referral, and the misdiagnosis rate was as high as 96.3% (131/136). Eight early clues for diagnosis were found, the frequency from high to low, large bacillus Callmette-Guer scar in 99 cases (70.5%), left axillary lymphadenopathy or calcification in 73 cases (52.5%), skin or other lymph node infections in 58 cases (41.7%), skin scars in 50 cases (36.0%), multiple lung nodules in 42 cases (30.2%), perianal abscess in 35 cases (25.2%), pulmonary Aspergillus infection in 26 cases (18.7%) and pulmonary Burkholderia infection in 15 cases (10.8%). A total of 120 cases of CGD were diagnosed by respiratory burst test during hospitalization, including 55 cases diagnosed before 2015 and 65 cases diagnosed after 2015. After using these 8 early diagnosis clues, the cases diagnosed after 2015 had shorter time of diagnosis and the length of stay and lower hospitalization charge than cases diagnosed before 2014, and the difference was statistically significant ((25±7) vs. (10±5) d, (29±7) vs. (18±6) d, (3.7×104±1.2×104) vs. (3.2×104±1.2×104) Yuan, t=13.763, 9.262, 2.381, all P<0.05). Conclusions: Patients with CGD are younger at onset and the diagnosis is delayed. Pulmonary infections are the most common. Large BCG scar, left axillary lymphadenopathy or calcification, skin or other lymph node infections, skin scars, multiple lung nodules, perianal abscesses, pulmonary Aspergillus infection and Burkholderia infection can help early diagnosis of CGD.

Adult-diagnosed Chronic Granulomatous Disease: The Need to Increase Awareness.

Chronic granulomatous disease is genetic disorder characterized by the inability of phagocytes to produce sufficient oxidative burst needed to kill intracellular organisms. Patients have recurrent, life-threatening infections involving multiple systems including the lungs, skin, lymph nodes, and liver. The majority of patients with chronic granulomatous disease are diagnosed in childhood although some may present in adulthood due to a milder phenotype. Unfortunately, these patients may also present with concomitant autoimmune diseases. We describe a 48-year-old woman with a history of immune thrombocytopenia and systemic lupus erythematosus on immunosuppressive therapy. She developed subsequent bacterial and fungal infections initially attributed to immunosuppressive drugs. Further evaluation revealed the diagnosis of chronic granulomatous disease. We review the diagnosis and treatment of chronic granulomatous disease in hopes to increase awareness of this disease in adulthood in order to initiate potential life-saving prophylactic antibiotics.

Abdominal Positron Emission Tomography Combined With Magnetic Resonance Imaging in Chronic Granulomatous Disease

Abdominal Positron Emission Tomography Combined With Magnetic Resonance Imaging in Chronic Granulomatous Disease

Clinical observation of Сhronic granulomatous disease in a 6-year-old child

Chronic granulomatous disease (CGD) is a hereditary disease caused by a genetic defect of violations of oxygen — dependent mechanisms of phagocytosis. Clinical manifestations of the disease are recurrent bacterial or fungal infections of the skin, hepatic abscesses, pneumonia, osteomyelitis, sepsis, meningitis et al. Most available laboratory method for the diagnosis of CGD is the test of histochemical nitro blue tetrazolium recovery (NBT-test). Allogeneic hematopoietic stem cell transplantation is considered a radical treatment for chronic granulomatous disease. The article presents a clinical observation of the manifestation of chronic granulomatous disease with an unfavorable outcome in a child aged 6 years.

Bacillus Calmette-Guérin (BCG) Infections at High Frequency in Both AR-CGD and X-CGD Patients Following BCG Vaccination.

Patients with chronic granulomatous disease (CGD) develop severe infections, including Bacillus Calmette-Guérin (BCG). Although the autosomal recessive CGD (AR-CGD) patients should hypothetically develop relatively fewer infections compared to the X-linked CGD (X-CGD) patients due to more residual reactive oxygen intermediates, the impacts of BCG vaccination on AR-CGD and X-CGD patients are unclear. Herein, we demonstrated the clinical features of BCG infections, treatments, and genetic factors in CGD patients after BCG vaccination under the Japanese immunization program. We collected data retrospectively from 43 patients with CGD and assessed their history of initial infection, age at diagnosis of CGD, BCG vaccination history, clinical course, treatment for BCG infections, and genetic mutations associated with CGD. Fourteen CGD patients avoided BCG vaccination because of other preceding infections and family history. Of 29 patients with CGD who received BCG vaccination, 20 patients developed BCG infections. Although the age at onset of initial infection in X-CGD patients was significantly younger than that in AR-CGD patients (P < .01), the onset and frequency of BCG infections were similar in X-CGD and AR-CGD patients. In X-CGD patients, BCG infections equally developed in the patients carrying missense, insertion, deletion, nonsense, and splice mutations of CYBB. All CGD patients with BCG infections were successfully treated with anti-tuberculous drugs. Although X-CGD patients develop severe infections at a younger age than AR-CGD patients, our data suggested that BCG infections develop at high frequency in both AR-CGD and X-CGD patients, regardless of genotype and mutant forms.